Case report: A novel occurrence of persistent left cranial vena cava coexisting with polycystic kidney disease in a cat

A 7-year-old castrated male Munchkin cat was presented with anorexia. This cat had been diagnosed with chronic kidney disease due to polycystic kidney disease. Tachycardia with a systolic murmur (grade III/VI) was auscultated and for further diagnosis, echocardiography was performed. Based on echocardiography, persistent left cranial vena cava (PLCVC) was suspected due to enlargement of the coronary sinus and confirmed by saline contrast echocardiography. The dilated coronary sinus compressed the left atrium, and left ventricular hypertrophy with the systolic anterior motion of the mitral valve, aortic regurgitation, and mitral regurgitation were identified. After medical management using atenolol, left atrial function and other hemodynamics of the heart were improved, including the disappearance of regurgitation and normalization of left ventricular wall thickness. This case report describes the echocardiographic characteristics, diagnostic procedures, and disease progression in a cat with PLCVC after medical management using atenolol. Additionally, this is the first report of a cat with PLCVC, coexisting with polycystic kidney disease

Olfactory marker protein regulates prolactin secretion and production by modulating Ca2+ and TRH signaling in lactotrophs

Olfactory marker protein (OMP) is a marker of olfactory receptor-mediated chemoreception, even outside the olfactory system. Here, we report that OMP expression in the pituitary gland plays a role in basal and thyrotropin-releasing hormone (TRH)-induced prolactin (PRL) production and secretion. We found that OMP was expressed in human and rodent pituitary glands, especially in PRL-secreting lactotrophs. OMP knockdown in GH4 rat pituitary cells increased PRL production and secretion via extracellular signal-regulated kinase (ERK)1/2 signaling. Real-time PCR analysis and the Ca2+ influx assay revealed that OMP was critical for TRH-induced PRL secretion. OMP-knockout mice showed lower fertility than control mice, which was associated with increased basal PRL production via activation of ERK1/2 signaling and reduced TRH-induced PRL secretion. However, both in vitro and in vivo results indicated that OMP was only required for hormone production and secretion because ERK1/2 activation failed to stimulate cell proliferation. Additionally, patients with prolactinoma lacked OMP expression in tumor tissues with hyperactivated ERK1/2 signaling. These findings indicate that OMP plays a role in PRL production and secretion in lactotrophs through the modulation of Ca2+ and TRH signaling. © 2018 The Author(s).1

Characterization of an Entner???Doudoroff pathway-activated Escherichia coli

Background Escherichia coli have both the Embden-Meyerhof-Parnas pathway (EMPP) and Entner-Doudoroff pathway (EDP) for glucose breakdown, while the EDP primarily remains inactive for glucose metabolism. However, EDP is a more favorable route than EMPP for the production of certain products. Results EDP was activated by deleting the pfkAB genes in conjunction with subsequent adaptive laboratory evolution (ALE). The evolved strains acquired mutations in transcriptional regulatory genes for glycolytic process (crp, galR, and gntR) and in glycolysis-related genes (gnd, ptsG, and talB). The genotypic, transcriptomic and phenotypic analyses of those mutations deepen our understanding of their beneficial effects on cellulosic biomass bio-conversion. On top of these scientific understandings, we further engineered the strain to produce higher level of lycopene and 3-hydroxypropionic acid. Conclusions These results indicate that the E. coli strain has innate capability to use EDP in lieu of EMPP for glucose metabolism, and this versatility can be harnessed to further engineer E. coli for specific biotechnological applications

A Protective Role for Heme Oxygenase-1 in INS-1 Cells and Rat Islets that are Exposed to High Glucose Conditions

Heme oxygenase-1 (HO-1) has been described as an inducible protein that is capable of cytoprotection via radical scavenging and the prevention of apoptosis. Chronic exposure to hyperglycemia can lead to cellular dysfunction that may become irreversible over time, and this process has been termed glucose toxicity. Yet little is known about the relation between glucose toxicity and HO-1 in the islets. The purposes of the present study were to determine whether prolonged exposure of pancreatic islets to a supraphysiologic glucose concentration disrupts the intracellular balance between reactive oxygen species (ROS) and HO-1, and so this causes defective insulin secretion; we also wanted to evaluate a protective role for HO-1 in pancreatic islets against high glucose levels. The intracellular peroxide levels of the pancreatic islets (INS-1 cell, rat islet) were increased in the high glucose media (30 mM glucose or 50 mM ribose). The HO-1 expression was induced in the INS-1 cells by the high glucose levels. Both the HO-1 expression and glucose stimulated insulin secretion (GSIS) was decreased simultaneously in the islets by treatment of the HO-1 antisense. The HO-1 was upregulated in the INS-1 cells by hemin, an inducer of HO-1. And, HO-1 upregulation induced by hemin reversed the GSIS in the islets at a high glucose condition. These results suggest HO-1 seems to mediate the protective response of pancreatic islets against the oxidative stress that is due to high glucose conditions

Comparison of Concomitant Mesalamine and Immunomodulator Therapy and Immunomodulator Monotherapy for Crohn’s Disease

Background. Although immunomodulators are increasingly used in Crohn’s disease (CD), a significant number of gastroenterologists still use 5-aminosalicylate (5-ASA) in combination with azathioprine (AZA) or 6-mercaptopurine (6-MP); there is limited evidence regarding the benefit of concomitant 5-ASA with AZA/6-MP compared with AZA/6-MP monotherapy for the treatment of CD. Study Design. A total of 106 patients who received AZA/6-MP for more than 3 months between January 1991 and May 2014 were identified retrospectively. Each patient was matched with 3 randomly selected controls who were treated with concomitant therapy during the same period. Results. The cumulative probabilities of steroid use at 5 and 10 years were 24.9% and 75.8% in the 5-ASA + AZA/6-MP group and 31.2% and 87.8% in the AZA/6-MP group, respectively (P=0.187). The cumulative probabilities of anti-TNF use, resectional surgery, and disease-related hospitalization were comparable between the groups. The younger age and the use of lower doses of immunomodulators were associated with higher requirement of rescue therapy. Conclusions. This study did not demonstrate that the concomitant use of 5-ASA with AZA/6-MP showed the proof or effect in terms of steroid requirements, anti-TNF use, resectional surgery, or disease-related hospitalization compared with that of AZA/6-MP alone

Methylsulfonylmethane Suppresses Breast Cancer Growth by Down-Regulating STAT3 and STAT5b Pathways

Breast cancer is the most aggressive form of all cancers, with high incidence and mortality rates. The purpose of the present study was to investigate the molecular mechanism by which methylsulfonylmethane (MSM) inhibits breast cancer growth in mice xenografts. MSM is an organic sulfur-containing natural compound without any toxicity. In this study, we demonstrated that MSM substantially decreased the viability of human breast cancer cells in a dose-dependent manner. MSM also suppressed the phosphorylation of STAT3, STAT5b, expression of IGF-1R, HIF-1α, VEGF, BrK, and p-IGF-1R and inhibited triple-negative receptor expression in receptor-positive cell lines. Moreover, MSM decreased the DNA-binding activities of STAT5b and STAT3, to the target gene promoters in MDA-MB 231 or co-transfected COS-7 cells. We confirmed that MSM significantly decreased the relative luciferase activities indicating crosstalk between STAT5b/IGF-1R, STAT5b/HSP90α, and STAT3/VEGF. To confirm these findings in vivo, xenografts were established in Balb/c athymic nude mice with MDA-MB 231 cells and MSM was administered for 30 days. Concurring to our in vitro analysis, these xenografts showed decreased expression of STAT3, STAT5b, IGF-1R and VEGF. Through in vitro and in vivo analysis, we confirmed that MSM can effectively regulate multiple targets including STAT3/VEGF and STAT5b/IGF-1R. These are the major molecules involved in tumor development, progression, and metastasis. Thus, we strongly recommend the use of MSM as a trial drug for treating all types of breast cancers including triple-negative cancers

Single nucleotide polymorphisms in bone turnover-related genes in Koreans: ethnic differences in linkage disequilibrium and haplotype

<p>Abstract</p> <p>Background</p> <p>Osteoporosis is defined as the loss of bone mineral density that leads to bone fragility with aging. Population-based case-control studies have identified polymorphisms in many candidate genes that have been associated with bone mass maintenance or osteoporotic fracture. To investigate single nucleotide polymorphisms (SNPs) that are associated with osteoporosis, we examined the genetic variation among Koreans by analyzing 81 genes according to their function in bone formation and resorption during bone remodeling.</p> <p>Methods</p> <p>We resequenced all the exons, splice junctions and promoter regions of candidate osteoporosis genes using 24 unrelated Korean individuals. Using the common SNPs from our study and the HapMap database, a statistical analysis of deviation in heterozygosity depicted.</p> <p>Results</p> <p>We identified 942 variants, including 888 SNPs, 43 insertion/deletion polymorphisms, and 11 microsatellite markers. Of the SNPs, 557 (63%) had been previously identified and 331 (37%) were newly discovered in the Korean population. When compared SNPs in the Korean population with those in HapMap database, 1% (or less) of SNPs in the Japanese and Chinese subpopulations and 20% of those in Caucasian and African subpopulations were significantly differentiated from the Hardy-Weinberg expectations. In addition, an analysis of the genetic diversity showed that there were no significant differences among Korean, Han Chinese and Japanese populations, but African and Caucasian populations were significantly differentiated in selected genes. Nevertheless, in the detailed analysis of genetic properties, the LD and Haplotype block patterns among the five sub-populations were substantially different from one another.</p> <p>Conclusion</p> <p>Through the resequencing of 81 osteoporosis candidate genes, 118 unknown SNPs with a minor allele frequency (MAF) > 0.05 were discovered in the Korean population. In addition, using the common SNPs between our study and HapMap, an analysis of genetic diversity and deviation in heterozygosity was performed and the polymorphisms of the above genes among the five populations were substantially differentiated from one another. Further studies of osteoporosis could utilize the polymorphisms identified in our data since they may have important implications for the selection of highly informative SNPs for future association studies.</p